In this study, zinc oxide nanoparticles synthesized from prickly pear fruit peel infusions (PP-ZnO-NPs) are in crystalline nature, 10–80 nm size range, high purity (Zn-80.37% and O-19.63%), possess relevant functional groups and optical properties. PP-ZnO-NPs mediated photocatalytic mitigation of 10 selected EDCs was higher (81–99%) under solar irradiation with fixed operative conditions. Further, the PP-ZnO-NPs efficiency on diluted (1:250 ratio) tannery wastewater was found to be potential by observed reductions of tested physic-chemical parameters. The toxicity threshold of ‘PP-ZnO-NPs’ was verified on both in vitro phytotoxicity on Vigna radiata (200 mg L−1) and cytotoxicity assay on Human cervix epithelioid carcinoma (HeLa) cell lines (568 µg mL−1). This study offers the ‘PP-ZnO-NPs’ as an environmentally benign and capable catalyst for ECs mitigation in the aquatic setups.